Loss of NPC1 enhances phagocytic uptake and impairs lipid trafficking in microglia.

Niemann-Pick type C disease is a rare neurodegenerative disorder mainly caused by mutations in Npc1, resulting in abnormal late endosomal/lysosomal lipid storage. Although microgliosis is a prominent pathological feature, direct consequences of NPC1 loss on microglial function remain uncharacterized. Previously, we have characterized microglial proteome alterations in the NPC1 KO mouse model (PXD019447). In order to investigate similar changes in humans, we have cultured monocyte derived macrophages ...

Niemann-Pick type C (NPC) disease is a rare neurodegenerative disorder mainly caused by autosomal recessive mutations in Npc1 which result in abnormal late endosomal/lysosomal lipid storage. Although microgliosis is one of the prominent pathological features, consequences of NPC1 loss on microglial function and disease outcome remain largely unknown. Here, we provide an in-depth characterization of microglial proteomic signatures and phenotypes in an NPC1-deficient (Npc1-/-) murine model. We ...

Niemann-Pick type C (NPC) disease is a rare neurodegenerative disorder mainly caused by autosomal recessive mutations in Npc1 which result in abnormal late endosomal/lysosomal lipid storage. Although microgliosis is one of the prominent pathological features, consequences of NPC1 loss on microglial function and disease outcome remain largely unknown. Here, we provide an in-depth characterization of microglial proteomic signatures and phenotypes in an NPC1-deficient (Npc1-/-) murine model. We ...